The preclinical discovery and development of rectal artesunate for the treatment of malaria in young children: a review of the evidence

ABSTRACT

Introduction

Plasmodium falciparum, the deadliest malaria parasite, kills hundreds of thousands of people per year, mainly young children in Sub-Saharan Africa. Artesunate suppositories are recommended as pre-referral malaria treatment in remote endemic areas for severely ill children to prevent progression of the disease and to provide extra time for patients until the definitive severe malaria treatment can be administered.

Areas covered

The authors provide an overview of the discovery of artesunate and its different formulations focusing on rectal administration, summarizing key studies concerning the pharmacokinetic, pharmacodynamic, safety, tolerability and efficacy of rectal artesunate leading to WHO recommendation and market authorization in Africa. In addition, studies on acceptance and adherence to rectal artesunate administration and the post-launch status are also covered.

Expert opinion

Efforts by ministries of health in malaria endemic countries together with international health organizations should establish and enforce guidelines to ensure the correct use of artesunate suppositories only as pre-referral medication in presumed severe malaria cases to minimize the risk of abuse as a monotherapy for treatment of uncomplicated malaria. The priority is to not jeopardize the efficacy of artesunate and to prevent resistance development against this valuable drug class in Africa.

KEYWORDS:

• Artesunate
• severe malaria
• Plasmodium falciparum
• pre-referral treatment
• rectal artesunate
• suppositories

Article highlights

• Rectal suppositories are an alternative treatment route, easy to administer, especially when oral therapy is hampered.

• Rectal artesunate at 10 mg/kg rapidly decreased malaria parasitemia.

• Single and multiple doses of rectal artesunate showed no significant difference in the time to clearance of malaria parasitemia.

• Rectal artesunate was first recommended by WHO in 2006.

• The first quality-assured artesunate suppositories were launched on the market in 2018.

• Rectal artesunate is now recommended by WHO as a single dose pre-referral treatment for children below 6 years of age in remote areas in Sub-Saharan Africa with suspected severe malaria before parenteral treatment can be started in a health care facility.

• Rectal artesunate should not be used to treat uncomplicated malaria to minimize the risk of development of parasite resistance against this valuable drug class in Africa.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The authors are funded by the University of Tübingen.